The objective of these studies is the clinical application of basic research and technological advances to the development of a patient "risk profile" for periodontal disease based upon environmental, microbiological and host response factors. We postulate that periodontal disease develops secondary to subgingival infection with specific periodontal pathogens transmitted from an exogenous source, and that this infection constitutes a key risk factor for periodontal disease. Furthermore, we hypothesize that defective production or function of host neutrophils is a risk factor in the etiology of severe and rapidly progressing forms of periodontal disease. Finally, we propose that elevations in salivary or serum antibody levels, especially IgM antibodies, precede periods of disease activity and may be risk factors or predictors for periodontal disease. To evaluate this model of periodontal disease and to assess other potential risk factors, we plan to randomly select a large adult sample to approximately 2,500 subjects between the ages of 25 and 54 years. These subjects will be examined at baseline and again at three year intervals in order to establish the clinical, microbiological, and host response factors which constitute a risk profile. Furthermore, we propose an in-depth study at six month intervals of a subgroup of approximately 10% of this population which we expect to have severe periodontal disease. This group will be intensively examined for bursts of periodontal disease activity, for shifts toward a periodontopathic flora, and for the presence and nature of neutrophil abnormalities and for the order and appearance of specific antibodies. Finally, we propose to study families and other household contacts of probands with severe periodontal disease for transmission of periodontal pathogens using molecular biologic techniques including restriction fragment length polymorphism, isoenzyme and antigenic fingerprinting analysis of bacterial isolates. These studies will provide significant new information concerning environmental factors such as stress-inducing events, distress, and systemic disease, microbial pathogens, neutrophils and antibodies. This data will have immediate application in targeting individual high-risk subjects for effective preventive therapy prior to the initiation of overt periodontal destruction.